The invention relates to a dry effervescent composition containing at least one vitaceutical, and optionally containing inulin and other active agents. The effervescent products optionally contain lubricants and essential oils and can generate magnesium malate, a therapeutic effector. The invention also encompasses methods of preparing the effervescent compositions of the invention.
Many types of formulations are available for administering medicaments to a subject. Solid dosage forms which are swallowed, such as tablets and capsules are useful because they provide quick and easy administration routes as well as accurate dosages. Many medicinal compositions, including vitamins, nutritional supplements and medicines have unpleasant tastes. These compositions can be administered in the form of a tablet or capsule to avoid unpleasant taste. Solid dosage forms, however, must disintegrate in the gastrointestinal tract and the medicament must dissolve before it is absorbed. As a result, absorption tends to be slower than from a liquid suspension and may be incomplete. Additionally, some subjects have difficulty swallowing tablets and capsules. Another draw-back of solid dosage forms is that tablets and capsules can only have a maximal size which can easily be swallowed and thus the dosage cannot be increased above that size. If more medicament is required, multiple tablets or capsules must be administered.
Medicinals can also be administered as liquids, chewables or formulations which dissolve in the mouth. In these instances, it is desirable to add a component which masks the taste of the bitter medicinals. Fruit flavoring mixed with sugars are often used.
Soluble medicaments administered in aqueous suspensions can also be used for administering medicaments. Aqueous suspensions are useful because they provide good bio-availability of the medicament. These preparations, however, often have limited shelf-life and it is difficult to accurately measure the dose of a medicament being provided. It is also difficult to mask the bitter taste of medicaments in this type of formulation.
In order to avoid some of the problems associated with administration of medicaments in the forms of solid dosages or aqueous suspensions, effervescent formulations can be used. Effervescent formulations usually require components which mask the taste because these formulations are dissolved in water prior to ingestion. Some effervescent formulations have been prepared using citrus flavoring. Other taste-masking substances include clove oil with a supportive flavor component or calcium carbonate, such as those described in U.S. Pat. No. 5,837,286. Clove oil is capable of masking the bitter taste of medicinals, particularly analgesics, expectorants, anti-tussives, decongestants or combinations thereof.
Effervescent formulations are well-known to those of ordinary skill in the art. These formulations include those described in U.S. Pat. Nos. 3,495,001; 3,518,344; 4,083,950; 4,783,331; 4,942,039; 5,824,339; 5,834,019; 5,962,022; 5,919,483; 5,912,012, and 5,869,095, the entire contents of which are hereby incorporated by reference. In general, effervescent formulations include an acid/base component such as edible organic acids such as citric acid and a carbonate or bicarbonate, lubricants, sweeteners, excipients, clarity-enhancing components, surfactants, emulsifiers, sorbitol, and mannitol to enhance compressibility.
When the effervescent formulation is dissolved in water, the base liberates carbon dioxide to produce the effervescent or fizzy characteristics of the formulation. The use of effervescent formulations to administer medicaments provides the advantage that disintegration of the medicament in the gastrointestinal tract is accomplished easily. Some of the disadvantages of prior art effervescent formulations include a difficulty with maintaining stability of hydrophobic compounds, the bad taste associated with certain medicaments, and the quick time with which the effervescent formulation must be consumed once it is mixed with water.
Another problem associated with the use of effervescent compositions has been the inability to incorporate acid-sensitive drugs because these compositions will hydrolyze or decompose while in contact with the acid of the effervescent system. Thus, these compositions are not stable for reasonable periods of time. Additionally, hydrophobic particles within the drug contained within the effervescent composition tend to leach out of the effervescent composition when it is mixed with water and deposit along the bottom or sides of the glass. Loratadine is an example of a hydrophobic active agent which is difficult to formulate in an effervescent composition.
Additionally, effervescent compositions are not a preferred composition for formulating hygroscopic medicaments. Hygroscopic medicaments take up and absorb moisture. When hygroscopic compounds in effervescent formulations are exposed to moisture they are quickly inactivated.
The invention is directed to effervescent compositions having improved properties. One of the effervescent compositions of the inventions is an effervescent formulation containing an inulin. The inulin increases the effervescence time, which would allow a subject to ingest the effervescent drink over a longer period of time. This would allow the subject to drink the effervescent formulation in a relaxed manner as a regular drink. Thus, one aim of the formulations of the invention, is to provide a composition which can be enjoyed in the form of a drink which tastes good and is enjoyable. This drink overcomes the difficulty associated with other forms of administering medicine, such as reluctance to swallow pills, bad taste associated with medicaments, and general problems associated with inconvenience due to the frequency and quantity of taking pills. Additionally, it is desirable to maintain intestinal health for maximal nutrient absorption and assimilation. Inulin can help to improve and maintain intestinal health, reducing stomach distress, increasing mineral absorption, helping to multiply the native gut microorganisms and decreasing pathogenic bacteria in the gut to promote nutrient assimilation.
The invention in other aspects relates to an effervescent formulation which produces a therapeutic agent when mixed with water. Thus the therapeutic agent is formed xe2x80x9cin situ.xe2x80x9d The effervescent compositions, according to this aspect of the invention, are capable of generating magnesium malate which has a therapeutic effect in the treatment of muscle soreness and has been used to promote muscle relaxation. In other aspects, the invention relates to methods of treating or preventing muscle soreness and/or promoting muscle relaxation by administering an effervescent composition of the invention.
According to yet another aspect of the invention, an effervescent composition containing a hygroscopic compound such as glucosamine is provided. Glucosamine is an active agent which has been used for the treatment of osteoarthritis. Because glucosamine is hygroscopic and oxidizes when exposed to air for long periods of time, it is predominantly available in hard gelatin capsule forms. Some tablet forms are also available. The tablets, however, suffer from deterioration due to moisture and oxygen. The novel effervescent formulations of the invention containing glucosamine and or other hygroscopic compounds are useful for delivering glucosamine for therapeutic purposes because they contain ingredients which help prevent the oxidation and deterioration of glucosamine within the formulation. The effervescent formulations include ascorbic acid which selectively protects glucosamine against oxidation by preferentially being oxidized. The formulation also contains sorbitol and/or inulin, which because they are more hygroscopic than glucosamine, selectively protect the glucosamine against moisture. Additionally, some of the most common side-effects of glucosamine are stomach distress, diarrhea, and nausea. Prebiotic inulin help to calm the gastrointestinal tract, thus minimizing the side-effects of glucosamine.
In another aspect, the invention is an effervescent formula which includes lubricants such as micronized fumaric and adipic acid without any additional lubricants. These compounds when used in a micronized form have the advantage that they develop lubricant properties. These compounds are usually used in effervescent formulations in combination with additional lubricants. When micronized fumaric acid or adipic acid are used according to the invention as the sole lubricant in the formulation.
The invention in other aspects relates to improved effervescent formulations including lubricants composed of vegetable oils flavored with essential oils such as orange, lemon, lime, etc. One problem associated with the effervescent formulations of the prior art is that when vegetable oils are used as lubricants, the vegetable oil floats to the top of the effervescent solution. Because the vegetable oil is on top it is the first part of the solution that is tasted. Many vegetable oils such as cotton seed oil which are good lubricants have an unpalatable flavor. The formulations of the invention include an essential oil mixed in to the vegetable oil. It was discovered according to the invention that the essential oils were completely capable of masking the unpleasant taste of the vegetable oil.
Thus, the invention in one aspect relates to an effervescent composition including a basic effervescent component; at least one pH neutralizing agent; and an inulin. In preferred embodiments the basic effervescent component is a carbonate or bicarbonate selected from the group consisting of sodium and/or potassium hydrogen carbonates and bicarbonates, calcium carbonate, magnesium carbonate, and amino acid carbonates. In other preferred embodiments the pH neutralizing agent is selected from the group consisting of L-tartaric acid, citric acid, lactic acid, malic acid, fumaric acid, aspartic acid, ascorbic acid, and amino acids.
In some embodiments the effervescent composition includes a vitaceutical, e.g., a vitamin, a mineral, an antioxidant, a nutraceutical etc. In some preferred embodiments the carbonate or bicarbonate is selected from the group consisting of magnesium carbonate and calcium carbonate and the pH neutralizing agent is malic acid. In other preferred embodiments the composition includes a hygroscopic compound such as glucosamine.
In other embodiments the effervescent compositions include a lubricant such as a micronized fumaric acid or adipic acid or a vegetable oil flavored with an essential oil such as orange, lemon, lime, etc.
The composition may also include other additives. For instance, in some embodiments the effervescent composition includes at least one sweetener, wherein the sweetener is selected from the group consisting of stevia, fructose, ribose, sucrose, tagatose, sucralose, malitol, erythritol, zylitol, acesulfame potassium, aspartame, and saccharine. In other embodiments the effervescent composition includes an excipient, a surfactant, an emulsifier, an osmotic pressure-regulator, and/or an electrolyte.
In other preferred embodiments the effervescent composition is composed of a carbonate or bicarbonate of sodium and potassium, citric acid, and inulin. In other embodiments effervescent composition is composed of magnesium carbonate, malic acid, and inulin.
In other preferred embodiments the effervescent composition include magnesium malate, riboflavin-5-phosphate, calcium pentothenate, peroxidine HCL boron chelate, copper gluconate, manganese gluconate, zinc sulfate, ascorbic acid and/or vitamin E.
According to another aspect the invention is an effervescent composition. The composition includes a basic effervescent agent; at least one pH neutralizing agent; and glucosamine. In one embodiment the composition also includes inulin and/or a vitaceutical.
In other aspects the invention is a method for treating or preventing muscle soreness. The method includes the steps of administering to a subject an effervescent composition of the invention, which produces magnesium malate in situ, in order to prevent or treat muscle soreness in a subject. The effervescent composition includes magnesium carbonate and malic acid which produce magnesium malate in situ.
In other aspects the invention is a method for treating or preventing osteoporosis. The method includes the steps of administering to a subject an effervescent composition of the invention, which produces calcium citrate in situ, in order to prevent or treat osteoporosis in a subject. The effervescent composition includes calcium carbonate and citric acid which produce calcium citrate in situ.
Each of the limitations of the invention can encompass various embodiments of the invention. It is, therefore, anticipated that each of the limitations of the invention involving any one element or combinations of elements can be included in each aspect of the invention.